We describe the use of a technique, TU-tagging, that allows identification of genes expressed in cells within their normal tissue environment. Stem cells are particularly sensitive to communication with other cells in complex tissues and this technique allows identification of genes expressed within stem cells or their surrounding "niche" cells under normal, physiologic conditions. We used TU-tagging to identify gene expression in endothelial cells of the brain (an important niche population for neural stem cells) and to identify gene expression in immune system cells versus niche cells of the spleen, using a blood stem cell transplantation model.